Michael Egnor is at it again. The guy is pretty much the energizer bunny of anti-evolution bullshit. This time, he’s purportedly refuting an article by Dr. Steven Novella, a Yale professor of neurology.

So, why am I butting my nose in to a discussion between two doctors? For two reasons:

First, because once again, Egnor pulls out his gibberish about information theory – and that’s definitely my turf.

Second, because ultimately, the argument that Dr. Egnor makes comes back to the silly way that he reduces to evolution to a tautology. As I’ve discussedseveraltimesbefore, Dr. Egnor formulates a trite, foolish tautology out of a description of natural selection, and then pretends that the entire theory of evolution is nothing more than his foolish tautology. Apparently, he’s convinced himself, and as a result, he creates arguments from it without
ever bothering to consider whether or not they make the slightest bit of sense. This latest
screed of his is the worst example of this that I’ve ever seen. And that’s saying a lot!

Anyway, enough intro. Let’s look at Egnor’s own words. Nothing I can say could possibly
be as damning as what he says himself. Replying to Novella’s description of how
Egnor publicly entered the argument over evolution, he says:

Actually, all I did was ask a question: how much biologically relevant information can Darwin’s mechanism of chance and necessity actually generate? I didn’t settle for hand-waving or for reassurances that “Darwin’s theory is a fact.” I wanted a measurement of biological complexity, with empirical verification, in a way that was meaningful to biology. I never got an answer to my question.

As regular readers of this blog will recall, that’s not exactly a true statement. Dr. Egnor first invoked information theory, demanded that he be shown a quantitative analysis
of how much information an evolutionary process could generate. And he was answered, with a detailed quantitative analysis of an evolutionary process in terms of Shannon’s information theory. That’s when he changed his terms, and started demanding a quantitative analysis of biological information – or as he terms is above, “biologically relevant” information. And since then, he has refused all requests for a definition of “biologically relevant” or “biological” information. I’ve dealt with this problem extensively before – it’s a classic shell game, where the questioner always wins, because he’s in control of the game. No matter how you respond, he can always say “You’re wrong, that’s not biological information.”

After that, he goes from bad to mind-numbingly, painfully awful:

Dr. Novella is missing a much better example of random mutation and natural selection that’s not metaphorical at all. Cancer is a test of Darwin’s theory. Cancer is real biological evolution by random mutation and natural selection, writ fast. There’s no reason to invoke encyclopedia typos or tractor engines in order to understand what “chance and necessity” can do to a living system. Brain tumors are perfect little Novellian “two-cycle engines” nestled inside the skull, “random mutations” coming out the ears, and “natural selection” like there’s no tomorrow (excuse the metaphors). Brain tumors are constantly generating new biological variation, and they are avatars of natural selection. They provide a tremendous spectrum of variation, from “variation jet-engines” like malignant glioblastoma multiforme to “variation tortoises” like benign pilocytic astrocytomas. Cancer wards are full of patients brimming with “two-stroke engines” of evolutionary change.

Dr. Novella, again:

…it is [easy] to imagine how shuffling around information, duplicating, and altering the information could easily result in meaningful and even useful new information.

The best real biological test of “shuffling around information, duplicating, and altering the information” is cancer. According to Dr. Novella’s reasoning, brain tumors ought to be generating quite a bit of “meaningful and even useful new information.” Better neuroanatomy and better neurophysiology ought to be popping up “easily.” Better frontal lobes and cognition, from cancer. Better temporal lobes and memory, from cancer. Better cerebellums and coordination, from cancer. If random mutations and natural selection–Dr. Novella’s “two stroke engine”–is the source of all functional integrated biological complexity, brain tumors ought to help our brains evolve in some way.

Perhaps Dr. Novella has data that show real evolutionary improvements in the brain caused by brain tumors. If he has, he should show us.

I’m just a rube, not a Darwinist from Yale. But I’ve never seen cancer make a brain better.

Dr. Egnor has become a victim of his own foolishness. He’s been so aggressive about pushing the idea that evolution is no more than his own reductionist tautology that he’s convinced himself that it’s really true – even to the point of ignoring everything that
he must know as a medical doctor.

As I’ve said before, you can reduce any proof to a tautology by simply wrapping all of the premises and inferences together into a single statement. Similarly, you can create
a tautology out of a scientific theory by combining the basic observations and inference steps that led to the theory into the statement of the theory.

Given a theory, you can state it as a tautology in a bunch of different ways. You can do it the correct way – in which case it doesn’t sound silly. To do that, you need to include statements about all of the relevant observations, and all of the necessary details of the theory. What you end up with really looks like a detailed argument leading up to the theory.

And then, you can do it the silly way. You can pull out a silly reductionist statement of the form “A therefore A”: “Things fall, therefore things fall”; “The individuals that survive to reproduce are the individuals that survive to reproduce”.

Egnor continually insists that evolution can be reproduced to that silly reductionist
version: “The individuals that survive to reproduce are the individuals that survive to
reproduce”. And that silly version, obviously, drops important parts of the theory – and
that’s exactly where Egnor’s problem comes from.

Remember, his reductionist tautology is “The individuals that survive to reproduce are
the individuals that survive to reproduce” – a reduction that is full of holes. He leaves
out everything else about the theory, and then falls into the hole that he put there
himself, all the while crowing about how that show’s that he’s correct.

What is he missing? What does evolution really say that he left out? It’s a
complex theory, but the part that’s relevant here is: It says that within a population,
changes will occur in the distribution of genes. Individuals with traits that make them
more successful at surviving to produce offspring pass those traits on to their
offspring.

Egnor’s cancer babble goes wrong because he forgets about that crucial “pass those traits on to their offspring”.

Cancer does produce a population of rapidly reproducing and rapidly mutating individuals. It’s certainly an example of a kind of evolutionary process: cells are reproducing wildly, and the ones that manage to survive to reproduce are the ones that survive to reproduce and pass their traits on to their offspring. But expecting the changes in cancer cells to produce any evolutionary changes in the host organism of the cancer is just incredible stupidity. Because changes in cancer cells don’t produce inheritable changes in the host. A brain cancer does not get to pass genes to the children of the host organism.

There’s a basic, fundamental distinction that Dr. Egnor must be familiar with – the distinction between germ cells and somatic cells. Germ cells are the cells which contain the genetic material that will be passed on to offspring; somatic cells are the rest of the cells of the body. Genetic changes in a cancer in somatic cells – i.e., pretty much all cancer cells – doesn’t affect the genes of the germ cells. The genetic changes of cancer are not heritable in terms of the reproduction of the host! The kind of selection that acts on the cells of a cancer that causes them to change over time isn’t the same selective pressure that’s working on the cells of the host, because cancer cell reproduction is not host reproduction; cancer cell mutations are not heritable mutations for the host!

In some sense, cancer can be viewed as a distinct species: instead of being a part of the host organism, they’re a parasite living inside of the host. The only children that cells of the cancer have are more cancer cells: the only way that a cancer cell passes genes to a child is by reproducing itself. Genetic changes in the cancer cells cannot produce a heritable change in the host organism – because genetic changes in cancer cells don’t change the genes of the host organisms reproductive cells. They don’t affect the genome of the host organism – only the genome of their own descendants: the other cancer cells that they produce.

When we talk about selection operating inside of a tumor, we’re talking about selection of cancer cells, selecting the
cells that are most successful at reproducing in the environment of the host: not selection that makes the survival and reproduction of the host more likely. The cancer cells that are most “successful” will eventually kill the host – so if anything, the success of cancer cells will cause a reduction in the fitness of the host.

And in fact, that’s something that we do observe. Organisms do possess traits that make them less likely to develop cancer.

Dr. Egnor really needs to stop his mouth from moving for a little while, and think
about what he’s saying. It’s really shocking to see an argument like this from someone who must know the difference between germ cells and somatic cells.

Comments

This is absolutely false. Egnor got plenty of responses to his question, showing him he was about equally ignorant of information theory and evolution. The thing is, every time he got an answer, he changed his question. He went from “show me an increase in information” to “show me new gene functions being formed” to “show me a demonstrable increase in a completely undefined quantity I choose to call “biological information.” He’s retreated into vacuity, where he can safely never be shown to be wrong (because he’s not even wrong, in the immortal words of Wolfgang Pauli).

He’s a dishonest scumbag. And it’s especially smarmy of him to say something like “I’m just a rube, not a Darwinist from Yale” when he’s been whoring his prestigious professorship at SUNY from day one of this debacle. Like someone on Orac’s blog said, just when you think Egnor has hit rock bottom, he pulls out the dynamite.

A pig-ignorant question from someone who has only a rudimentary understanding of how cancer spreads: can cancer spread to germ cells? I’m thinking particularly of testicular and ovarian cancer, which is at least anatomically colocated near scads of germ cells. Given the extremely debilitating effects of cancer, and the likelihood that mutated germ cells would simply be unviable, I’m assuming this wouldn’t translate into a statistically significant source of mutation in the host organism anyways, but I’m curious as to whether it’s even a theoretical possibility.

Hate to start these comments off with a semi-negative but this is interesting and relevant:

“One biologist, Leigh Van Valen, has written that Lacks’ cancer cells have evolved into a self-replicating, single-cell life-form and has proposed HeLa cells be given the new species name of Helacyton gartleri. The cells are a genetic chimera of human papillomavirus 18 (HPV18) and human cervical cells and now have a distinct, stable, non-human chromosome number. His 1991 suggestion has not been followed, nor, indeed, been widely noted. With near unanimity, evolutionary scientists and biologists hold that a chimeric human cell line is not a distinct species, and that tumorigenesis is not an evolutionary process.[15] However, at least two transformed mammalian cell lines cause communicable diseases: Devil facial tumour disease and Canine transmissible venereal tumor.” [ http://en.wikipedia.org/wiki/Henrietta_Lacks#Helacyton_gartleri
]

So on one hand, apparently evolutionary scientist don’t recognize cancer cells as a distinct species, but the idea has been seriously considered but some before (and I’d be inclined to agree). Also, the later two examples in the quote do imply that cancer can be reproductively successful for themselves, if not for the host.

Regardless, your point about the difference between germ and somatic cells function in natural selection still stands.

I’m not a biologist, and I’m proceeding from memory, but in most cancers, the cancer itself is caused by a damage to the error-correction mechanism of the DNA, as well as the control mechanisms that normaly control the rate of replication.

In consequence, not only the cancerous cells reproduce at a high rate, but they show an incredibly high rate of mutations. Soon the chromosomes are no longer recognizable. Please correct me if I’m misleading.

This situation is extremely different from the normal reproduction of organisms, or cell, where the DNA is identical to the parent cell, except for some relatively rare level of mutation.

In tumors, as I understand it, the DNA gets mutated/damaged at every replication giving stranger and stranger cells. What is curious is that so many of those cells manage to stay “alive”, despite their grossly abnormal DNA.

Not being a biologist, I would think so. But consider that the hallmark of a cancer cell is that it gives up its normal function and start multiplying. All germ cells mature through a rather complicated process, which the cancer cell gives up.

(And even small problems in sperms and ova makes them inviable or produce spontaneous abort. AFAIK most fertilizations end up as aborts for that reason.)

the later two examples in the quote do imply that cancer can be reproductively successful for themselves

And of the two cancer pathogens, it seems the canine kind is appropriately aggressive so the host will transmit the disease by normal sexual behavior. (The tasmanian devil kind is transmitted by aggressive behavior, so it may be beneficial for the pathogen to be painful.)

Not that Egnor would care for the difference to normal cancers.

What is curious is that so many of those cells manage to stay “alive”, despite their grossly abnormal DNA.

By my meager understanding the cells that survive immune system attacks to become cancers are those that turn off the normal death program in the cell so no signal (external or internal) can kill it. They are inherently harder to kill.

In large cancers I believe the inner cells dies from lack of oxygen. IIRC the ability to trigger arterial growth by releasing required growth factors is another benefit that some cancers pull off.

Btw, doesn’t the question answer itself? Those cancer cells that grow fastest will dominate, as in all evolution. (Cue Egnor: “tautology”.) AFAIK cancer adapts to some of the chemical treatments if they aren’t followed up by other activities.

If the cells can be hugely mutated it probably shows that relaxing the requirement to obey the normal behavior opens up to very relaxed constraints.

Wow. I used to think that creationists ascribed to a rather Lamarckian picture of evolution, so of course it’s easy to poke holes in that. But I think that’s wrong. This crazy mix of craze isn’t even Lamarckian. It’s, well… not even wrong.

Torbjörn, still under the caveat that I don’t know what I’m talking of,
it is not the immune system “responsibility” to kill cancerous cells, those are still body cells, albeit strange ones.
There is a mechanism, apoptosis, which detects gross cellular abnormality, and trigger an orderly cell suicide. In cancerous cells the apoptotic pathway is disabled.
And yes, cancer cells (in human hosts) undergo a tremendously rapid evolution, to no avail, because cancer tends to kill the host in various ways, either by emitting biological poisons of the bloodstream, by impairing organ function, by destroying whole organs, and by other numerous other ways. Even when a slow cancer doesn’t kill its host, it is doomed to extinction when its host dies of old age.
It could be argued that one cancer could find a way to be transmitted for individual to individual, but the very instability of cancer cells make it unlikely it could ever result in a “viable” contagious disease as such.
It is not impossible, in the abstract, that a cancerous-type process, in a very simple organism like say, fungus, may have led to a new, viable and stable, organism with a changed DNA. It is merely highly unlikely, has not yet been observerved, and is not expected to be a major evolutionary mechanism. The cancerous process is in itself adverse to the _fixation_ of useful traits.

It is not the immune system “responsibility” to kill cancerous cells, those are still body cells, albeit strange ones.

You could be correct. At the very least it seems to be, or have been, controversial.

This is how one site that has a commercial interest positively frames the issue:

If a gene has become an oncogene, the cell in which it is located may begin to produce unusually large amounts of one of its normal proteins or to manufacture an altered form of that protein. If an anti-oncogene has been rendered inactive, the cell containing it can no longer produce a normal protein whose function is to suppress cancer. On some rare occasions, a normal cell becomes cancerous when a particular virus enters the cell and introduces an oncogene into the genome of the host cell. Once any of these deviations in normal protein production and/or function has occurred, the size, shape, surface characteristics, or morphology and behavior of the cell becomes altered. Thus, it becomes a cancer cell that is distinguishable from a normal cell.

Thus, the theory of immunosurveillance remained controversial until an important scientific article entitled “IFN-gamma and lymphocytes prevent primary tumor development and shape tumor immunogenicity” was published in the journal Nature on April 26, 2001. This breakthrough article was authored by Robert D. Schreiber, Ph.D., and his colleagues at Washington University School of Medicine, St. Louis, MO, in collaboration with Lloyd J. Old, M.D., of the Ludwig Institute for Cancer Research and Memorial Sloan-Kettering Cancer Center, New York, NY. The experimental evidence presented in their paper unambiguously showed that the immune system can and often does prevent tumors from developing, and thus plays a strong protective role against cancer.

[Bold added. CRI “has relied on support from individuals, corporations, and foundations to fund cutting-edge research seeking to develop new and safer ways to control cancer.”]

It could be argued that one cancer could find a way to be transmitted for individual to individual, but the very instability of cancer cells make it unlikely it could ever result in a “viable” contagious disease as such.

I’m not sure what you mean here. Jon’s comment presented the two usually mentioned examples of communicable cancer.

The cancerous process is in itself adverse to the _fixation_ of useful traits.

Nicely put, with the exception that in some environments it seems it will be fixated. Again, see Jon’s comment for three examples, and the interpretation among biologists.

While the changes made by a brain cancer cell cannot be inherited by the host, they could modify the function of the hosts brain. Indeed, some insanities are caused by brain tumors.

Perhaps Dr. Egnor was simply asking if these changes in the host brain would be beneficial? If mutation “Easily” causes improvement, this is a fair question. Except, of course, that the mutation that makes a cell cancerous is not normally the mutation that would make it a better brain cell.

Is it even possible that a cancerous tissue would be better at it’s job than the non-cancerous tissue? Well, hormone-secreting tumors can secrete more growth or stress hormone than an ordinary gland. I suppose ‘more’ could be viewed as ‘better’, except that the high levels growth hormone cause the disease acromegaly and high levels of stress hormone cause Cushings syndrome.

That being the case, we can imagine a set of cancerous brain cells that do something better or at least more than ordinary brain cells. Could this excess of whatever make the host a more fit organism?

It wouldn’t be heritable, but it could, just possibly, be more fit. Has this ever been observed?

The problem with your scenario is that cancer cells reproduce for their own advantage. There’s no selective pressure that makes cancer cells that are more functional for the host more likely to survive and reproduce. And in fact, in a typical cancer cell population, a cancer cell that provided a beneficial effect for the host would likely be selected against, because the most successful cancer cells are the ones that reproduce the most, and doing something for the host would divert energy away from reproduction, slowing its growth.

In the long run, obviously, cancer is a dead end: no matter how successful the cancer is, once it kills its host, its dead. But evolution doesn’t guarantee survival. It doesn’t have any ability to look into the future and see what’s going to happen later. It only selects what’s likely to survive and reproduce in its present environment – and for a cancer, that’s its living host. The fact that it’s going to kill it doesn’t matter.

There is more than babbling in his argument. Or it can be thought of. Imagine the primordial soup, where autotroph bacterias lived. Is it possible that a single strain of predator bacterias wiped out all other life on the planet and died themselves from a lack of food? It is, IMHO. Why not?
So we have something like succesive search, as opposed to the width-search of darwinian evolution. Some life appears, then it’s destroyed by evolved predators, then some other kind of life appears, and it’s destroyed too, and finally after 4*10^9 years there appears a life that is able to support homeostasis in respect to predators. Or, more precisely, this time differential equation “hunter-prey” hadn’t reached one of its extremities bofore a new hunter evolved, thus making the whole system quasi-stable.

“It could be argued that one cancer could find a way to be transmitted for individual to individual, but the very instability of cancer cells make it unlikely it could ever result in a “viable” contagious disease as such.”

Possibly scary thought: veterinary researchers have found an actual instance of this. It’s a sexually-transmitted cancer afflicting dogs. It’s not like HPV, which is a virus which can cause cancer in humans. No, with this disease, the actual cancerous cells transfer to a new host. Tumors *literally* as parasites. So while it seems so improbable as to be not worth worrying about, it has already occurred at least once…

Dr. Egnor’s comment makes perfect sense from a DI point of view (likely why it’s so pathetic as real science). It’s that whole thing about mutation never being beneficial, ’cause it deviates from the Designer’s perfect plan. (If the plan’s so perfect, why does it allow deviation? Ah well, I’m sure the DI or the Vatican will find a scientific answer for us in Scripture.) Carroll and many others have answered this over and over with examples of (heritable) gene duplication, etc., but that gets the usual ID response of fingers in the ears and “Neener neener neener!” loudly repeated.

Oh, you could also possibly mean a cancer that induces other cells to become cancers. It hasn’t been observed AFAIK, but it could be possible. (Or at least, in the form of viruses and perhaps other pathogens (with genomes) causing cancers, induction is possible in a roundabout fashion. Especially retroviruses open up several such paths as I understand it.)

Um, but the same objection remains, I think. Communicability means a possibility for fixation.

He also seems to be following the weird axiom that an evolutionary process necessarily improves an organism, as in “I’ve never seen cancer make a brain better”. To take a grossly simplistic view of evolution, sometimes a disease improves a species by killing a subset of the members of that species.

Cancer may well make the aggregated brains of the human species better… but not during Egnor’s lifetime unfortunately, so there’s no hope for HIS brain.

The Xenogenesis trilogy by Octavia Butler revolved around the extraterrestrial traders coming to Earth, and the most valuable thing we had to sell them was Cancer. Yesterday was Jackie Robinson Day in Los Angeles. Jackie Robinson, Octavia Butler, and Presidential Candidate Bill Richardson all hail from Pasadena. Must be some weird radiation from Caltech…

“A pig-ignorant question from someone who has only a rudimentary understanding of how cancer spreads: can cancer spread to germ cells? I’m thinking particularly of testicular and ovarian cancer, which is at least anatomically colocated near scads of germ cells.”

With the exception of some virally induced cancers, cancer doesn’t spread from one cell type to another. Rather, cancer cells derived from the original (“primary”) tumor spread throughout the body.

There are some germ cell tumors that act a bit like stem cells, and can even differentiate into different types of tissues. I’ve never heard of the tumor cells giving rise to viable sperm or ova. In some cases, however, it has been possible to disaggregate the cells from a mouse tumor of this type, mix them with cells of an embryo, and end up with an apparently healthy chimeric mouse in which some cells are derived from the tumor, indicating that the tumor cells have somehow been “reset” by the embryonic environment. Sometimes those cells give rise to germ cells in the chimera, and by appropriate breeding it is possible to breed an animal whose “parent” is a tumor cell. At one point, this was being developed as a way of creating genetic disease models, since the cancer cells could be propagated for a while in culture and subjected to selection pressures to derive specific types of mutations. However, I believe this approach was overtaken by transgenic technology, which is both a more powerful and easier approach to creating specific mutations.

Quite a few years back, the science fiction writer Theodore Sturgeon wrote a short story, “When you care, when you really love,” based upon the premise that it might be possible to clone a human being using a similar germ-tumor based method, anticipating the subsequent development of other cloning technologies.

“Science Daily — Cancer is a natural consequence of human evolution. Our genes have not developed to give us long and happy lives. They are optimized to copy themselves into the next generation – irrespective of our personal desires. According to Jarle Breivik, an associate professor at the University of Oslo, Norway, we are therefore unlikely to find a final solution to cancer….”

I tried and apparently failed to post a excerpt of, and URL of, a press release entitled: “No Solution To Cancer: Have Our Genes Evolved To Turn Against Us?”
Source: University Of Oslo
Date: April 17, 2007
“…Doing research at the Institute of Basic Medical Sciences, Breivik explores the connection between cancer development and Darwinian evolution. In a recent interview with Scientific American, and the research magazine Apollon, published by the University of Oslo, he concludes that ‘Cancer is a fundamental consequence of the way we are made. We are temporary colonies made by our genes to propagate themselves to the next generation. The ultimate solution to cancer is that we would have to start reproducing ourselves in a different way….'”

“…This research shows how the environment influences the selection of genes inside of the body and is identical to the principle that Darwin found to explain the origin of species.”

“The body is not a static system. Our cells are in a constant state of development, and new genetic variants arise every day. Many of these mutants are removed by the immune system but, sooner or later, a cell will break through the defences and develop into a tumour of wild-growing renegades….”

“Cancer development is an evolutionary process within the multicellular organism, but it is also related to the general process of evolution through the generations. Life begins when our parent’s genes are united in the zygote. These genes have been selected through millions of generations for their ability to create a functional organism, but few days after fertilization the genes split up in two different directions. Some end up in the germ cells (sperm and ova) that will bring them to the next generation, while the rest end up in the somatic cells that make up our body. The somatic cells are initially programmed to cooperate, but as we age and new mutations arise, the evolutionary process will favour cells that break ranks and propagate freely within the body. Thus, according to Breivik, the division between germ cells and somatic cells represents the Darwinian explanation to cancer …”

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties.
RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network.
CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations.

Incidentally, when linking to Discovery Institute or other crackpot drivel, I believe including the rel=”nofollow” attribute in the A HREF tag will prevent your link from increasing the target site’s Google rank.

Another way (with Good Math and Good Biology) to understand actual protein evolution is to look at the tertiary structure (the 3-D shape the molecule folds to) and look at similarities and differences between the shape of similar proteins in different organisms, over time.

Recent results are very illuminating, and put some hard numbers on the ID hand-waving about how few random mutations of a protein are allegedly viable.

Science Daily — The present can tell you a lot about the past, but you need to know where to look. A new study appearing this month in Genome Research reveals that protein architectures – the three-dimensional structures of specific regions within proteins – provide an extraordinary window on the history of life.

[Crop sciences professor Gustavo Caetano-Anollés, back row center, describes contemporary protein architectures as “molecular fossils” or “historical imprints” that mark important milestones in evolutionary history. His research team compiled a global census of protein architectures, and used these relics to plot the emergence, diversification and refinement of each of the three superkingdoms of life: Archaea, Bacteria and Eukarya. Members of the team: front row, left to right, Jay Mittenthal, cell and developmental biology, and undergraduate Derek Caetano-Annollés; back row, Liudmila Yafremava and Minglei Wang, postdoctoral students in crop sciences. (Credit: Photo by L. Brian Stauffer)]

In the study, researchers at the University of Illinois describe contemporary protein architectures as “molecular fossils” or “historical imprints” that mark important milestones in evolutionary history. The research team compiled a global census of protein architectures, and used these relics to plot the emergence, diversification and refinement of each of the three superkingdoms of life: Archaea, Bacteria and Eukarya.

All proteins are composed of architectural elements, called domains, which can be identified by their structural and functional similarities to one another. Protein domains are the gears, belts, springs and motors that allow the larger protein machinery to function as it should. Every protein contains one or more of them, and proteins that perform very different tasks can contain identical domains.

Protein domains are grouped into what are called fold families and fold superfamilies. Members of a fold superfamily may differ in their underlying amino acid sequences, but retain structural and functional similarities and are evolutionarily related. Fold superfamilies are grouped together into broad categories, called folds.

The new study tracks the evolution of folds and fold superfamilies from the ancient world to the present.

Protein folds turn out to be reliable markers of evolutionary events because they are quite stable over time, said Gustavo Caetano-Anollés, a professor of crop sciences and a principal investigator on the study. Even mutations in the genes that code for them rarely change their three-dimensional structures.

“Structures are highly conserved because they were important discoveries in the history of the world,” Caetano-Anollés said. “It’s very difficult to come up with a new design to do something in a way that an existing structure cannot already do.”

The idea that protein folds are highly refined and profoundly flexible machines is supported by the fact that there are so few of them. Scientists have identified only about 1,000 folds and 1,500 fold superfamilies across all the organisms for which full genomes have been sequenced. Many of these protein folds are found in every organism. Other folds appear only in certain subsets of organismal life.

The Illinois team’s findings add a new dimension to a long and contentious debate about the earliest stages of evolutionary divergence. By looking at protein architectures across all organisms for which genomic information is available, the team found evidence that the archaeal microbes, the one-celled organisms that inhabit some of the most forbidding environments on the planet, were the first to emerge as an evolutionarily distinguishable group. Their evidence: The repertoire of architectures that would one day belong to the superkingdom known as the Archaea was the first to lose a fold. That fold, a huge class of protein fold superfamilies, simply disappeared from the archaeal lineage altogether.

Eventually, more and more folds joined the list of architectures abandoned by the Archaea, in what the authors describe as a process of “reductive evolution.” The folds belonging to organisms that eventually evolved into what we now call bacteria and the multicellular eukaryotes also began to lose folds, but they started downsizing their repertoires much later than the Archaea.

Prior to this, the authors write, the world of protein folds was large and diverse, containing many of the fold architectures still in use today. This was the time of the “communal ancestor,” before the emergence of superkingdoms and the myriad organisms that would eventually populate each group.

This overview of protein architectures adds to the picture of how the superkingdoms emerged and diverged. The Archaea jettisoned many of the folds that had been part of their original heritage.

As a group, the bacteria lost fewer folds, although those that were parasites or obligate parasites retained only a minimalist repertoire of folds. Their strategy was to take advantage of the protein machinery available in their hosts.

The multicellular Eukarya, a group that includes humans, retained the largest repertoire of fold architectures.

“We are the keepers of everything. We have the largest repertoire that there is,” Caetano-Anollés said. The eukaryotes’ evolution into large, multicellular bodies that could live in diverse environments relied on an extensive library of protein architectures, he said.

The new study divides the evolution of protein architectures into three phases. First, there was a common world, with a large collection of protein folds available to all. The researchers call this a period of architectural diversification.

Next came a period, called superkingdom specification, during which the three superkingdoms emerged. The third phase, organismal diversification, saw an explosion of inventiveness in protein architectures, particularly among the Eukarya.

Caetano-Anollés stressed that any attempt to build an evolutionary tree of life is limited by the type of data used to populate the tree. He compared the task to that of writing a history of building architecture by analyzing the changes over time that occurred in a single building component, such as the window.

“The window is a good element for studying the history of buildings,” he said. “But it can be misleading because windows may have their own pace of historical change.”

Caetano-Anollés said he believes his team’s tree of protein architectures is robust because it is rooted in two axiomatic statements that seem to yield consistent and reliable results: First, the structure of protein folds is more stable than their genetic – and protein -sequences. Second, the folds that are the most common in life are also the most ancient.

The researchers suggest that the evolution of protein architectures is a key mechanism by which the three superkingdoms of life emerged from a communal ancestor. Adopting some protein architectures while abandoning others, perhaps in response to environmental pressures, may have been the first steps on the path of evolutionary divergence.

The research team included postdoctoral researchers Minglei Wang and Liudmila Yafremava, undergraduate student Derek Caetano-Anollés, and professor emeritus in cell and developmental biology Jay Mitthenthal. Gustavo Caetano-Anollés and Jay Mittenthal are affiliated with the Institute for Genomic Biology.

Note: This story has been adapted from material provided by University of Illinois at Urbana-Champaign.